Transmucosal and transepithelial drug delivery system

Abstract

Described herein is a transmembrane delivery system comprising: a pharmaceutically active moiety; and a polypeptide of up to 20 amino acids in length comprising a continuous region of at least 2, more typically at least 4 basic amino acids. Typically the system comprises a polypeptide which has the formula: (B) n (A) m where B is a basic amino acid A is an acidic amino acid, m and n are integers, and n is at least 4, and m is less than n.

1 . A transmembrane delivery system comprising:
 a pharmaceutically active moiety; and   a polypeptide containing about 20 amino acids or less in length comprising a continuous region of at least 2 basic amino acids.   
     
     
         2 . The system according to  claim 1 , wherein the polypeptide forms nanosomes of about 2 to about 5,000 nm. 
     
     
         3 . The system according to  claim 1 , wherein the basic amino acids are linked to an amino acid sequence defining a binding moiety. 
     
     
         4 . The system according to  claim 1 , wherein the polypeptide has the formula:
   (B) n (A) m      where B is a basic amino acid   A is an acidic amino acid, and   m and n and integers and   n is at least 4   m is less than n.   
     
     
         5 . The system according to  claim 1 , wherein the polypeptide consists of basic amino acids. 
     
     
         6 . The system according to  claim 1 , wherein each basic amino acid is independently selected from the group consisting of arginine (R), lysine (K) and histidine (H). 
     
     
         7 . The system according to  claim 4 , wherein the each acidic amino acid is independently selected from the group consisting of aspartate (D) and glutamate (E). 
     
     
         8 . The system according to  claim 1 , wherein the pharmaceutically active moiety is a polypeptide, a glycoprotein or a nucleic acids. 
     
     
         9 . The system according to  claim 1 , wherein the pharmaceutically active moiety has a molecular weight of about 500 kDa or less. 
     
     
         10 . The system according to  claim 9 , wherein the pharmaceutically active moiety is Decorin. 
     
     
         11 . The system according to  claim 1 , wherein the pharmaceutically active moiety and polypeptide are covalently bound or non-covalently bound. 
     
     
         12 . The system according to  claim 11 , wherein the polypeptide is attached to the pharmaceutically active moiety via an attachment moiety which covalently attaches the polypeptide and pharmaceutically active moiety, the attachment moiety comprising; succinimidyl succinate, N-hydroxy succinimide, succinimidyl propionate, succinimidyl butanoate, propionaldehyde, acetaldehyde, tresylate, triazine, vinyl sulfone, benzotriazole carbonate, maleimide, pyridyl sulfide, iodoacetamide, succimidyl carbonate, maleimidyl or avidin/biotin, or a combination thereof. 
     
     
         13 . The system according to  claim 1 , additionally comprising one or more penetration enhancers selected from the group consisting of polyethylene glycols, fatty acid esters, diacids or monomethyl esters, or a combination thereof. 
     
     
         14 . The system according to  claim 1 , adapted to be applied to eyes or mucous membranes. 
     
     
         15 . The system according to  claim 1 , in the form of a skin patch, eye drops, nose drops or a suppository. 
     
     
         16 . The system according to  claim 1 , for use in the treatment of disease. 
     
     
         17 . The system according to  claim 16 , wherein the disease is eye disease. 
     
     
         18 . A method for treating disease, the method comprising applying a pharmaceutically effective amount of the system according to  claim 1 . 
     
     
         19 . A method for transporting a pharmaceutically active moiety across skin, the surface of an eye or a mucosal membrane, the method comprising applying to the skin, surface of the eye or membrane the system according to  claim 1 . 
     
     
         20 . The system according to  claim 1 , wherein the continuous region is at least 4 basic amino acids.